The objective of this project is to determine the normal mechanism of regulation of globin messenger RNA synthesis in bone marrow cells. Specific regulatory factors, either protein or RNA molecules, will be sought which influence the transcription of the individual human or sheep globin genes. These studies will be applied to chromatin from cells of patients with beta thalassemia to provide further insight into molecular defect in this disease. Reconstitution of bone marrow non-histone proteins to non-erythroid chromatin may provide a means to assay specific non-histone protein fractions for regulatory factors. Purification of the globin genes by fractionation of chromatin will be pursued in an effort to obtain DNA fragments also containing sequences of nucleotides which may interact with regulatory proteins.